Today radioactive tracers, so called radiotracers, for single-photon emission computed tomography (SPECT) and positron emission tomography (PET), and radiopharmaceuticals for therapeutic uses are produced in hot laboratories or special production facilities, which are run under regulatory rules in order to meet good manufacturing practice (GMP) production criteria. The hot laboratories are large facilities, generally divided into separate sections and working compartments, mostly denoted hot cells, with room for operators, laboratories with radiation-shielding and storehouse for radioactive waste.
The hot cells in the hot laboratories are chambers with strong radiation shielding of high-density materials. The interior surfaces of the hot cells are typically lined with stainless steel coated by oil paints or polyethylene films to facilitate decontamination.
A hot laboratory is typically part of a radiochemical laboratory complex, requiring extensive planning to house the extensive facility. High demands are also put on the staff working in the hot laboratory with significant documentation in order to meet, among others, the regulatory demands on ventilation classification, radiation safety and measurements of biologics, all with the emphasis on the safety for personal and the production of the radiotracers and the radiopharmaceuticals for the patients within the facilities
Today qualification of hot laboratories according to GMP is typically made by independent companies or regulatory bodies to test and qualify the protocols and documentation of the hot laboratories. All important information is then documented in standard operation procedure (SOP) for the hot laboratories as well as for the production of the various labeled products. Such qualifications are generally performed two to three times per year.
It is obvious that building and running hot laboratories is very expensive and requires significant amount of regulatory documentation and control, which thereby put limitations to which medical facilities that have access to radiotracers and other radioactively labeled substances for diagnosis or therapy. Furthermore, the need for separate hot laboratories limits the type of radioactive isotopes (radionuclides) that can be used in the radiotracers and labeled substances to have a half-life that is long enough to allow transport of the radiotracers or labeled substances from the hot laboratories to the PET/SPECT or treatment center and still have sufficient radioactivity for efficient diagnosis or treatment of a patient. This means that in practical applications fluorine-18 (18F) with a half-life of about 110 minutes is commonly used as radionuclide. However, there is a general need to be able to use other radioisotopes with a much shorter half-life, such as 11C, 13N or 15O with half-life of about 20, 13 and 2 minutes, respectively. These radionuclides, however, need on-site production facilities.
Thus, there is a need for a system that can be used to manufacture radiotracers and other radioactive substances in a safe and cost-effective manner. It is a further need that such a system is miniaturized so that it can be arranged in or close to the PET/SPECT or treatment center to enable usage of radioisotopes with relatively short half-lives. These needs are also present for the manufacture of other, non-radioactive, substances, in particular for various diagnostic and therapeutic substances.
U.S. Pat. No. 7,829,032 discloses a microfluidic device that can be used in a fully automated synthesis system of radioactive compounds for PET-imaging in a fast, efficient and compact manner. The system is in the form of an automated, stand-alone, microfluidic instrument for a multi-step chemical synthesis of radiopharmaceuticals.
US 2011/0008215 discloses a system for a fully automated synthesis of radioactive compounds for PET-imaging in an efficient, compact and safe-to-the-operator manner. The system comprises a hot component unit and a cold component unit provided as separate units that are operatively connected to each other.
The systems disclosed in the above two patent documents enable miniaturization of the synthesis of radiotracers and other radioactively labeled substances. However, the prior art systems are not designed to meet the high demands of GMP in the synthesis process.